{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:56:43Z","timestamp":1792789003735,"version":"4.5.0"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2024-I2M-ZH-019"],"award-info":[{"award-number":["2024-I2M-ZH-019"]}]},{"award":["2024-I2M-ZH-019"],"award-info":[{"award-number":["2024-I2M-ZH-019"]}],"id":[{"id":"https:\/\/ror.org\/04gswd735","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation of China","award":["82604076"],"award-info":[{"award-number":["82604076"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["823B2028"],"award-info":[{"award-number":["823B2028"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"award":["82604076"],"award-info":[{"award-number":["82604076"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["823B2028"],"award-info":[{"award-number":["823B2028"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Postdoctoral Fellowship Program of CPSF","award":["GZC20251897"],"award-info":[{"award-number":["GZC20251897"]}]},{"name":"the Postdoctoral Fellowship Program of CPSF","award":["2025M772880"],"award-info":[{"award-number":["2025M772880"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sci.","Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Transcranial magneto-acoustic stimulation (TMAS) is an emerging multiphysics neuromodulation modality that introduces magneto-acoustically induced currents into ultrasound-based neural stimulation. However, how this coupled physical input is converted into neuronal recruitment and measurable biological responses remains insufficiently understood. This study aimed to establish a computational\u2013experimental framework for quantifying TMAS-induced neural activation across stimulation dose, spike timing, and calcium-related response domains. Methods: The model combined ultrasound-induced membrane mechanics, charge-based neuronal electrophysiology, pressure-dependent calcium-current modulation, and a Lorentz-force-mediated current source for TMAS. Regular-spiking excitatory neurons and low-threshold-spiking inhibitory interneurons were simulated to estimate excitation thresholds, firing latency, and spike-pattern transitions. Two model-informed stimulation conditions were examined using in vitro calcium imaging, in vivo hippocampal fiber photometry, and c-Fos\/microtubule-associated protein 2 (MAP2) immunofluorescence. Results: TMAS reduced the half-maximal effective dose relative to transcranial ultrasound stimulation by 71.4\u201376.3% in regular spiking neurons and 51.5\u201358.2% in low-threshold spiking interneurons, while shortening firing latency and expanding burst-response domains. Experimentally, near-threshold TMAS produced larger peak calcium responses and greater c-Fos\/MAP2 immunoreactivity than TUS. Conclusions: TMAS enhances neuronal responsiveness more efficiently than TUS by reducing excitation thresholds, improving spike-timing responses, and reshaping firing-pattern transitions. Consistent with the overall computational comparison, experimental measurements showed greater neuronal activation under TMAS than under TUS at matched ultrasound parameters.<\/jats:p>","DOI":"10.3390\/brainsci16090973","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:01:00Z","timestamp":1789405260000},"page":"973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational\u2013Experimental Characterization of Transcranial Magneto-Acoustic Stimulation for Dose-Efficient Neural Activation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9402-5395","authenticated-orcid":false,"given":"Ruxin","family":"Tan","sequence":"first","affiliation":[{"name":"School of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangxuan","family":"Chu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9945-2765","authenticated-orcid":false,"given":"Ren","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1111-0232","authenticated-orcid":false,"given":"Haojun","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/s41591-022-02197-0","article-title":"New and emerging approaches to treat psychiatric disorders","volume":"29","author":"Scangos","year":"2023","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s43586-024-00368-6","article-title":"Low-intensity focused ultrasound for human neuromodulation","volume":"4","author":"Legon","year":"2024","journal-title":"Nat. Rev. Methods Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41386-023-01699-w","article-title":"Transcranial focused ultrasound (tFUS): A promising noninvasive deep brain stimulation approach for pain","volume":"49","author":"Badran","year":"2024","journal-title":"Neuropsychopharmacology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2110807","DOI":"10.1016\/j.clinph.2025.2110807","article-title":"Transcranial magneto-acoustic stimulation suppresses the power and coherence of beta-oscillations in parkinsonian rat model with improvement motor performance","volume":"177","author":"Zhang","year":"2025","journal-title":"Clin. Neurophysiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1007\/s13311-019-00732-5","article-title":"Transcranial Magneto-Acoustic Stimulation Improves Neuroplasticity in Hippocampus of Parkinson\u2019s Disease Model Mice","volume":"16","author":"Wang","year":"2019","journal-title":"Neurotherapeutics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115352","DOI":"10.1016\/j.expneurol.2025.115352","article-title":"Modulatory effects of transcranial magneto-acoustic stimulation on behavior and corticostriatal transmission of oscillatory activity in a mouse model of Parkinson\u2019s disease induced by MPTP","volume":"392","author":"Xu","year":"2025","journal-title":"Exp. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1475-925X-2-6","article-title":"Can ultrasound be used to stimulate nerve tissue?","volume":"2","author":"Norton","year":"2003","journal-title":"Biomed. Eng. Online"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.neuroscience.2024.01.028","article-title":"Effects of transcranial magneto-acoustic stimulation on cognitive function and neural signal transmission in the hippocampal CA1 region of mice","volume":"556","author":"Zhang","year":"2024","journal-title":"Neuroscience"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"084301","DOI":"10.1088\/1674-1056\/25\/8\/084301","article-title":"A new brain stimulation method: Noninvasive transcranial magneto-acoustical stimulation","volume":"25","author":"Yuan","year":"2016","journal-title":"Chin. Phys. B"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, H., Zhou, X., Cui, D., Liu, R., Tan, R., Wang, X., Liu, Z., and Yin, T. (2019). Comparative Study of Transcranial Magneto-Acoustic Stimulation and Transcranial Ultrasound Stimulation of Motor Cortex. Front. Behav. Neurosci., 13.","DOI":"10.3389\/fnbeh.2019.00241"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1109\/TNSRE.2024.3395641","article-title":"Study on Improving the Modulatory Effect of Rhythmic Oscillations by Transcranial Magneto-Acoustic Stimulation","volume":"32","author":"Tan","year":"2024","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhou, X., Liu, S., Wang, Y., Yin, T., Yang, Z., and Liu, Z. (2019). High-Resolution Transcranial Electrical Simulation for Living Mice Based on Magneto-Acoustic Effect. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01342"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"0130","DOI":"10.34133\/research.0130","article-title":"Transcranial Magneto-Acoustic Stimulation Attenuates Synaptic Plasticity Impairment through the Activation of Piezo1 in Alzheimer\u2019s Disease Mouse Model","volume":"6","author":"Chu","year":"2023","journal-title":"Research"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, C., Tan, R., Zhou, X., Wang, R., Wang, X., Ma, R., Chu, F., Li, Y., Yin, T., and Liu, Z. (2024). Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094651"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.brs.2025.02.019","article-title":"Biophysical effects and neuromodulatory dose of transcranial ultrasonic stimulation","volume":"18","author":"Nandi","year":"2025","journal-title":"Brain Stimul."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1016\/j.neuron.2024.07.002","article-title":"Optimized ultrasound neuromodulation for non-invasive control of behavior and physiology","volume":"112","author":"Murphy","year":"2024","journal-title":"Neuron"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.ultrasmedbio.2012.09.009","article-title":"Effective Parameters for Ultrasound-Induced In Vivo Neurostimulation","volume":"39","author":"King","year":"2013","journal-title":"Ultrasound Med. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1523\/JNEUROSCI.1458-17.2018","article-title":"Ultrasound Elicits Behavioral Responses through Mechanical Effects on Neurons and Ion Channels in a Simple Nervous System","volume":"38","author":"Kubanek","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1038\/s41467-021-22743-7","article-title":"Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation","volume":"12","author":"Yu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.ultrasmedbio.2023.11.004","article-title":"Ultrasound Modulates Calcium Activity in Cultured Neurons, Glial Cells, Endothelial Cells and Pericytes","volume":"50","author":"Newman","year":"2024","journal-title":"Ultrasound Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2006980118","DOI":"10.1073\/pnas.2006980118","article-title":"Ultrasound activates mechanosensitive TRAAK K+ channels through the lipid membrane","volume":"118","author":"Sorum","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41467-022-28040-1","article-title":"Focused ultrasound excites cortical neurons via mechanosensitive calcium accumulation and ion channel amplification","volume":"13","author":"Yoo","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2300291120","DOI":"10.1073\/pnas.2300291120","article-title":"The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation","volume":"120","author":"Zhu","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, M., Ling, Z., Wang, P., and Jian, X. (2021). The Influence of Transcranial Magnetoacoustic Stimulation Parameters on the Basal Ganglia-Thalamus Neural Network in Parkinson\u2019s Disease. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.761720"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"055006","DOI":"10.1088\/2057-1976\/aa84c8","article-title":"Theoretical analysis of the effects of transcranial magneto-acoustical stimulation on neuronal firing rhythm and Ca2+ concentration with Chay neuron model","volume":"3","author":"Yuan","year":"2017","journal-title":"Biomed. Phys. Eng. Express"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"108372","DOI":"10.1016\/j.isci.2023.108372","article-title":"Effects of focused ultrasound in a \u201cclean\u201d mouse model of ultrasonic neuromodulation","volume":"26","author":"Guo","year":"2023","journal-title":"iScience"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yuan, Y., Pang, N., Chen, Y., Wang, Y., and Li, X. (2017). A Phase-Locking Analysis of Neuronal Firing Rhythms with Transcranial Magneto-Acoustical Stimulation Based on the Hodgkin-Huxley Neuron Model. Front. Comput. Neurosci., 11.","DOI":"10.3389\/fncom.2017.00001"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yuan, Y., Chen, Y., and Li, X. (2016). Theoretical Analysis of Transcranial Magneto-Acoustical Stimulation with Hodgkin-Huxley Neuron Model. Front. Comput. Neurosci., 10.","DOI":"10.3389\/fncom.2016.00035"},{"key":"ref_29","first-page":"1","article-title":"Effect of Transcranial Ultrasonic-Magnetic Stimulation on Two Types of Neural Firing Behaviors in Modified Izhikevich Model","volume":"54","author":"Zhang","year":"2018","journal-title":"IEEE Trans. Magn."},{"key":"ref_30","first-page":"011004","article-title":"Intramembrane Cavitation as a Predictive Bio-Piezoelectric Mechanism for Ultrasonic Brain Stimulation","volume":"4","author":"Plaksin","year":"2014","journal-title":"Phys. Rev. X"},{"key":"ref_31","first-page":"101604","article-title":"Low-intensity ultrasound activates transmembrane chloride flow through CFTR","volume":"37","author":"Wen","year":"2024","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1007\/s12264-025-01420-5","article-title":"Piezo1 Mediates Ultrasound-Stimulated Dopaminergic Neuron Protection via Synaptic Vesicle Recycling and Ferroptosis Inhibition","volume":"41","author":"Xu","year":"2025","journal-title":"Neurosci. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1152\/physrev.00010.2012","article-title":"T-Type Ca2+ channels in Normal and Abnormal Brain Functions","volume":"93","author":"Cheong","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1152\/physrev.00018.2002","article-title":"Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels","volume":"83","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e59548","DOI":"10.7554\/eLife.59548","article-title":"Nonlinearities between inhibition and T-type calcium channel activity bidirectionally regulate thalamic oscillations","volume":"9","author":"Lu","year":"2020","journal-title":"eLife"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hayut, I., Fanselow, E.E., Connors, B.W., and Golomb, D. (2011). LTS and FS Inhibitory Interneurons, Short-Term Synaptic Plasticity, and Cortical Circuit Dynamics. PLoS Comput. Biol., 7.","DOI":"10.1371\/journal.pcbi.1002248"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"eaay3302","DOI":"10.1126\/science.aay3302","article-title":"Coupling of NMDA receptors and TRPM4 guides discovery of unconventional neuroprotectants","volume":"370","author":"Yan","year":"2020","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111425","DOI":"10.1016\/j.isci.2024.111425","article-title":"Identification and development of TRPM4 antagonists to counteract neuronal excitotoxicity","volume":"27","author":"Pironet","year":"2024","journal-title":"iScience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13705","DOI":"10.1073\/pnas.1511740112","article-title":"Phosphorylation of the Cav3.2 T-type calcium channel directly regulates its gating properties","volume":"112","author":"Blesneac","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"046007","DOI":"10.1088\/1741-2552\/ab1685","article-title":"Understanding ultrasound neuromodulation using a computationally efficient and interpretable model of intramembrane cavitation","volume":"16","author":"Lemaire","year":"2019","journal-title":"J. Neural Eng."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mi, J., Zhang, S., Lu, X., and Xu, Y. (2025). Transcranial Magneto-Acoustic Stimulation Enhances Cognitive and Working Memory in AD Rats by Regulating Theta-Gamma Oscillation Coupling and Synergistic Activity in the Hippocampal CA3 Region. Brain Sci., 15.","DOI":"10.3390\/brainsci15070701"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"115364","DOI":"10.1016\/j.bbr.2024.115364","article-title":"Transcranial magneto-acoustic stimulation enhances motor function and modulates cortical excitability of motor cortex in a Parkinson\u2019s disease mouse model","volume":"480","author":"Zhang","year":"2025","journal-title":"Behav. Brain Res."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/9\/973\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:12:52Z","timestamp":1789618372000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/9\/973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["brainsci16090973"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16090973","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]}}}